Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2

Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27 trimethylation (H3K27me3), a hallmark of gene silencing. Here we report the crystal structures of an active PRC2 complex of 170 kilodaltons from the yeast Chaetomium thermophilum in both basal and stimulated states, which contain Ezh2, Eed...

Full description

Saved in:

Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) 2015-10, Vol.350 (6258), p.291-291
Main Authors:	Jiao, Lianying, Liu, Xin
Format:	Article
Language:	eng
Subjects:	Allosteric Regulation Amino Acid Sequence Catalysis Catalytic Domain Chaetomium - genetics Chaetomium - metabolism Contact Crystal structure Crystallography, X-Ray Fungal Proteins - antagonists & inhibitors Fungal Proteins - chemistry Fungal Proteins - metabolism Gene Silencing Genes Histones Histones - metabolism Humans Jumonji Domain-Containing Histone Demethylases - metabolism Lysine Methylation Molecular Sequence Data Mutation Neoplasms - genetics Peptides Polycomb Repressive Complex 2 - antagonists & inhibitors Polycomb Repressive Complex 2 - chemistry Polycomb Repressive Complex 2 - metabolism Protein Structure, Tertiary RESEARCH ARTICLE SUMMARY S-Adenosylhomocysteine - chemistry S-Adenosylhomocysteine - metabolism Stimulation Transcription, Genetic Yeast
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27 trimethylation (H3K27me3), a hallmark of gene silencing. Here we report the crystal structures of an active PRC2 complex of 170 kilodaltons from the yeast Chaetomium thermophilum in both basal and stimulated states, which contain Ezh2, Eed, and the VEFS domain of Suz12 and are bound to a cancer-associated inhibiting H3K27M peptide and a S-adenosyl-l-homocysteine cofactor. The stimulated complex also contains an additional stimulating H3K27me3 peptide. Eed is engulfed by a belt-like structure of Ezh2, and Suz12(VEFS) contacts both of these two subunits to confer an unusual split active SET domain for catalysis. Comparison of PRC2 in the basal and stimulated states reveals a mobile Ezh2 motif that responds to stimulation to allosterically regulate the active site.
ISSN:	0036-8075 1095-9203